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L A Cohen

Publications and source records attributed to L A Cohen.

At least 37 records · Page 2Linked to original sources
PubMed1997

Role of the extracellular loops of the thyrotropin-releasing hormone receptor: evidence for an initial interaction with thyrotropin-releasing hormone.

Thyrotropin-releasing hormone (TRH), like most small ligands, appears to bind within the seven transmembrane-spanning helices (TMs) of its G protein-coupled receptor (TRH-R). A role for the extracellular loops (ECLs) of TRH-R has not been established. We substituted residues in the ECLs of TRH-R and show that Tyr-181 is important for high-affinity binding because its substitution leads to a 3700-fold lowering of the estimated affinity compared to wild-type TRH-R. Using TRH analogues, we provide evidence that there is a specific interaction between Tyr-181 in ECL-2 and the pyroGlu moiety of TRH. It was previously suggested that the pyroGlu of TRH may interact with Asn-110 in TM-3 and with Asn-289 in ECL-3; N110A and N289A TRH-Rs exhibit similar apparent affinities that are only 20-30-fold lower than wild-type TRH-R. To better understand these findings, we analyzed a computer-generated model which predicts that the ECLs form an entry channel into the TRH-R TM bundle, that Tyr-181 projects into this channel and that the pyroGlu of TRH cannot simultaneously interact with residues in the TMs and ECLs. Kinetic analysis showed that the association rate of [Ntau-methyl-His]TRH with N289A TRH-R is slower than with wild-type TRH-R and largely accounts for the lower apparent affinity; the association rate with N110A TRH-R is similar to that of wild-type TRH-R. These data are consistent with the idea that there are initial interactions between TRH and the residues of a putative entry channel of TRH-R. We suggest that a role of the ECLs in all G protein-coupled receptors for small ligands may be to initially contact the ligand and allow entry into a TM binding pocket.

Animals↗
PubMed1997

Breast cancer: weighing the evidence for a promoting role of dietary fat.

It has been hypothesized that a high-fat diet promotes the development of postmenopausal breast cancer. This contention is supported by data showing high international correlations between fat intake and breast cancer rates, modest positive associations with a high-fat diet in case-control studies, and animal model studies that have consistently demonstrated that dietary fat influences mammary cancer development at several stages in the carcinogenic process. A number of plausible biologic mechanisms have been suggested that may explain such promotional effects. In contrast, dietary fat intake is unrelated to the risk of breast cancer in cohort studies. The conflicting findings from cohort studies have created uncertainty regarding nutritional recommendations and breast cancer prevention. After reviewing key scientific findings that are relevant to this issue, the following conclusion is drawn: In the absence of data from dietary intervention trials, the weight of available evidence suggests that the type and amount of fat in the diet is related to postmenopausal breast cancer and that the inability to detect associations within populations (cohort studies) is because of measurement error and the relative homogeneity of diets measured. It is expected that the results from intervention trials will clarify this issue.

Animals↗
PubMed1997

The challenges of assessing fat intake in cancer research investigations.

Ecologic comparison of the incidence of cancer (eg, largescale differences between countries in the incidence of breast, prostate, and colon cancer) can be explained best by substantial differences in the intake of dietary fat. Additionally, there is a vast amount of animal and mechanistic data that strongly supports the hypothesis that ditary fat, independent of caloric intake, appears to have a major effect on the incidence and mortality rates for cancer. Yet, results from human case and cohort studies are inconsistent in linking carcinogenesis with fat intake. This is due to several factors. Reported intakes may not reflect previous long-term intakes and may be con-founded by several sources of error, including memory and estimates of portion size. Additionally, ongoing media reports of adverse health effects from high-fat diets may impart a social desirability bias to self-reporting of fat intake. These factors may be significant when investigating the relationship between dietary intake and cancer. Studies have shown considerable error in self-reported dietary data, with under-estimations in energy intake ranging from 3% to 18%. Such a wide range likely is due to differences in dietary assessment methodologies, which highlights the need to continue to develop improved techniques of data collection to relate nutrition better to health outcomes. The Women's Intervention Nutrition Study (WINS) is investigating the effect of dietary fat on the incidence of recurrence and survival in women with early-stage breast cancer. WINS is employing the multiple-pass 24-hour telephone recall system along with enhanced quality control measures to assess dietary intake. This dietary assessment method is particularly applicable when comparing two populations when one population is treated by an extensive dietary intervention.

Animals↗
PubMed1997

Ondansetron reduces nausea and vomiting after paediatric adenotonsillectomy.

The efficacy, safety and resource implications of a single intravenous dose of ondansetron (0.1 mg.kg-1, maximum 4 mg) were assessed in a multinational, multicentre, randomized, double-blind, placebo-controlled trial of 427 children aged 1-12 years, undergoing tonsillectomy with/without adenoidectomy. Emesis (retching and/or vomiting) and nausea were analysed separately. Significantly more ondansetron-treated children had no episodes of emesis (127/212 (60%) vs 100/215 (47%); P = 0.004) and experienced no postoperative nausea (135/211 (64%) vs 108/213 (51%); P = 0.004) in the first 24 h. Ondansetron also reduced the number of emetic episodes (P < 0.001), the time to the first emetic episode (P < 0.001) and overall nausea severity (P = 0.003). Significantly fewer ondansetron-treated children were rescued or withdrawn from the study (5% vs 10%; P = 0.042). Fewer ondansetron-treated patients required nursing intervention (34% vs 45%; P = 0.007) and the average intervention time was significantly shorter (4.6 vs 8.1 minutes; P = 0.001). Resources used to manage PONV were significantly reduced by ondansetron (43% vs 57%; P = 0.014).

Adenoidectomy↗
PubMed1996

Wheat bran and psyllium diets: effects on N-methylnitrosourea-induced mammary tumorigenesis in F344 rats.

BACKGROUND: Experimental and epidemiologic evidence suggests that increased dietary fiber is associated with decreased breast cancer risk. Little is known about the role played by different types of fiber and, particularly, mixtures of soluble and insoluble fibers similar to those consumed by human populations in reducing breast cancer risk. High intake of fiber may suppress bacterial hydrolysis of biliary estrogen conjugates to free (absorbable) estrogens in the colon and thus may decrease the availability of circulating estrogens necessary for the development and growth of breast cancers. PURPOSE: The purpose of this study was to evaluate the effect of wheat bran (an insoluble fiber) and psyllium (a soluble fiber) alone and in combination on overall estrogen status, on fecal bacterial beta-D-glucuronidase (a key diet-responsive estrogen-deconjugating enzyme) activity, and on the induction of mammary tumors in rats treated with N-methylnitrosourea (MNU). METHODS: One hundred fifty virgin female F344 rats were fed the NIH-07 diet from 28 days of age until 50 days of age; they were then given a single dose (40 mg/kg of body weight) of MNU by tail vein injection. Three days later, they were randomly assigned to one of five experimental dietary groups (30 animals per group). Soft, white wheat bran (45% dietary fiber content) and psyllium (80% dietary fiber content) were added to a modified (high-fat) American Institute of Nutrition (AIN)-76A diet at the following percents, respectively: 12% + 0% (group 1), 8% + 2% (group 2), 6% + 3% (group 3), 4% + 4% (group 4), and 0% + 6% (group 5). Blood, urine, and feces were collected and analyzed by radioimmunoassay techniques for estrogens. Cecal contents were analyzed for bacterial beta-D-glucuronidase activity. After 19 weeks on the experimental diets, the rats were killed, and mammary tumors were counted and classified by histologic type. Cumulative tumor incidence was evaluated by the Kaplan-Meier life-table method and the logrank test. Tumor number was evaluated by the chi-squared test of association, and tumor multiplicity was evaluated by the Mantel-Haenszel chi-squared test. All statistical tests were two-tailed. RESULTS: As the level of psyllium relative to that of wheat bran increased, the total tumor number and multiplicity of mammary adenocarcinomas in rats decreased as a statistically significant linear trend across groups 1-5 (P < .05). Compared with the group given wheat bran alone, the group given the 1:1 (wheat bran:psyllium) combination had maximum protection against mammary tumorigenesis, while the groups given the 4:1 or 2:1 (wheat bran:psyllium) combination or psyllium alone had intermediate protection. No statistically significant differences in circulating estrogens or urinary estrogen excretion patterns were observed among the five experimental groups. Fecal estrogen excretion, however, decreased with increasing levels of psyllium (P < .01), and cecal beta-D-glucuronidase activity exhibited a decreasing trend with respect to the increasing psyllium content of the diet across groups 1-5 (P < .01). CONCLUSIONS: The addition of a 4%:4% mixture of an insoluble (wheat bran) fiber and a soluble (psyllium) fiber to a high-fat diet provided the maximum tumor-inhibiting effects in this mammary tumor model. Although increasing levels of dietary psyllium were associated with decreased cecal bacterial beta-D-glucuronidase activity, these changes were not reflected in decreased circulating levels of tumor-promoting estrogens. Therefore, the mechanism(s) by which mixtures of soluble and insoluble dietary fibers protect against mammary tumorigenesis remains to be clarified.

Animals↗
PubMed1996

Dose-response effects of dietary fiber on NMU-induced mammary tumorigenesis, estrogen levels and estrogen excretion in female rats.

The dose-related effects of the fiber-rich isolate, soft white wheat bran (SWWB), and the pure fiber, cellulose, on N-nitrosomethylurea (NMU)-induced mammary tumorigenesis was assessed in F344 female rats. SWWB (45% total dietary fiber, TDF) was added to the AIN-76A high-fat diet at 9, 12, 15 and 18%; cellulose (98% TDF) was added to the same diet at 4.5, 6, 7.5 and 9%, to give equivalent amounts of TDF. The experimental diets were fed 3 days post-NMU and continued for a period of 25 weeks, at which time the experiment was terminated and tumors enumerated. It was found that significant inhibition of mammary carcinoma occurred only at 9% SWWB, non-significant inhibition occurred at 12% SWWB, and no inhibition was seen at higher doses. Cellulose-fed animals exhibited consistently higher tumor yields regardless of dose. The difference in tumor yields between the 9% SWWB group and the remaining seven groups was attributable to an increased incidence in tumors characterized histologically as intraductal proliferation and ductal carcinoma in situ in the latter. Analysis of blood, urine and fecal estrogens was conducted to test whether dietary fiber exerted its tumor-inhibiting effect by altering the enterohepatic recycling of estrogens. Although SWWB, in general, lowered urinary estrogen excretion, increased fecal estrogen excretion and lowered blood estrogens, there was no consistent correlation between the amount of SWWB consumed, estrogen status and tumor yields. These results suggest that (i) wheat bran fiber at 9%, or minor constituents associated with it, contain anti-promoting properties that cellulose lacks; (ii) SWWB appears to exert its effects by suppressing the clonal expansion phase of mammary carcinogenesis; (iii) there is an upper limit (12-15% w/w) to the protective effects of SWWB; and (iv) the effects of SWWB on mammary tumorigenesis may not be attributed to alterations in the enterohepatic recycling of estrogens.

Animals↗
PubMed1996

Does the elimination of Medicaid reimbursement affect the frequency of emergency department dental visits?

In an attempt to save costs, the state of Maryland in February 1993 eliminated Medicaid reimbursement to dentists for treatment of adults with dental emergencies. The authors analyzed data from the University of Maryland Hospital's emergency department to determine if this change resulted in increased use of the emergency department by Medicaid recipients for treatment of dental conditions. After the policy change, the rate of dental visits to the emergency department by Medicaid recipients increased by 21.8 percent. This increase occurred during the same period in which the percentage of all emergency department visits by Medicaid recipients was decreasing.

Adult↗
PubMed1996

Evaluation of a one-day AIDS continuing education course.

The effectiveness of a one-day acquired immune deficiency syndrome (AIDS) continuing education course for dentists and hygienists was evaluated using pretest, posttest, and six-month follow-up questionnaires. There was a general, though not statistically significant, increase in the percentage of respondents who reported they planned to be immunized against hepatitis B, and a statistically significant increase in dentists' perceptions of the percentage of their patients at risk for AIDS. The percentage of respondents who believed the private practice setting is the preferred practice site for treating healthy patients with human immunodeficiency virus (HIV) increased, though the increase was not statistically significant. Six-month follow-up results found a significant increase in the percentage of respondents who reported being immunized against hepatitis B. Other posttest results were maintained at the six-month follow-up. These results support the contention that a traditional lecture approach in AIDS continuing dental professional education can be beneficial.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Inhibition of growth of human breast carcinoma xenografts by energy expenditure via voluntary exercise in athymic mice fed a high-fat diet.

The purpose of this study was to assess the effect of energy expenditure, via voluntary exercise, on growth of xenografts of human breast carcinomas in athymic nude mice. Sedentary and exercising athymic nude mice bearing subcutaneous grafts of MDA-MB231 human breast carcinomas were fed daily a purified high-fat diet at 10% less than ad libitum to ensure an equal quantity of diet (energy) consumption for each sedentary and exercising mouse. The sedentary and exercising mice were housed singly; the exercising mice had, in addition, access to an activity wheel (24 hrs/day). Growth of human breast carcinomas (carcinoma volumes) was evaluated during a five-week periods. Mean running activities of individual mice over the five-week period ranged from < 1 to 7.9 miles/day. Growth of the human breast carcinomas was significantly inversely correlated with the mean number of miles that each mouse ran per day (p < 0.018). Upon separation of these mice into two running groups, i.e., those that averaged 2.7-4.7 miles/day and those that averaged > 4.7 miles/day, carcinoma growth was 83% of sedentary controls in the former group (p = 0.305) and 59% of sedentary controls in the latter group (p = 0.039). These results provide evidence that energy expenditure, via voluntary use of an activity wheel, can reduce significantly the growth of human breast carcinomas maintained in athymic nude mice.

Animals↗
PubMed1994

Interactions between 4-HPR and diet in NMU-induced mammary tumorigenesis.

The present study was designed to determine whether the chemopreventive effect of the synthetic retinoid N(4-hydroxyphenyl)retinamide (4-HPR) on mammary tumorigenesis was influenced by diet. Three diets were used: the closed-formula grain-based Wayne Lab Blox, the open-formula grain-based NIH-07, and the casein-based semipurified AIN-76A. Groups of 25 virgin female F-344 rats were fed the experimental diets beginning one week before a single injection of N-methyl-N-nitrosourea (NMU, 45 mg/kg body wt i.v.) at 50 days of age. The experimental design was as follows: Group 1, unsupplemented AIN-76A; Group 2, AIN-76A supplemented with 4-HPR starting seven days before NMU until termination (-7); Group 3, AIN-76A supplemented with 4-HPR seven days after NMU until termination (+7); Group 4, Wayne (no 4-HPR); Group 5, Wayne (4-HPR, -7); Group 6, Wayne (4-HPR, +7); Group 7, NIH-07; Group 8, NIH-07 (4-HPR, -7). 4-HPR [782 mg/kg diet (2 mM)] was given to all supplemented groups. Termination was 25 weeks post-NMU. Analysis of tumor incidence, multiplicity, and latency indicated that 1) control rats fed the AIN-76A diet exhibited significantly higher mammary tumor yields than rats fed unsupplemented natural-ingredient diets (Wayne and NIH-07) and 2) 4-HPR inhibited mammary tumor development in the two grain-based diets but enhanced tumor development in the AIN-76A diet. Animals fed the AIN-76A diet gained weight to a greater extent than those fed the Wayne or NIH-07 diets and exhibited lower levels of circulating 4-HPR.

Animals↗
PubMed1994

Nutrition and prostate cancer: a proposal for dietary intervention.

In this review, we consider the evidence from geographic and metabolic epidemiology and laboratory studies with human prostate cancer cell lines and animal models that emphasizes the need for the development and implementation of a dietary intervention trial in prostate cancer patients. It is concluded that such a trial should include a reduction in total fat consumption to 15% of total calories and supplementation of the diet with selenium, vitamin E, and a soya product. The low-fat intervention would provide an appropriate reduction in the intake of any specifically targeted dietary fatty acid, such as linoleic acid or alpha-linolenic acid.

Animals↗
PubMed1994

Single oral dose ondansetron in the prevention of postoperative nausea and emesis. The European and US Study Groups.

In two placebo-controlled, double-blind, multicentre studies, the efficacy and safety of single oral doses of ondansetron 4 mg, 8 mg and 16 mg were evaluated for the prevention of postoperative nausea and vomiting in female inpatients. For the total study populations, 26% (European study) and 32% (US study) of placebo-treated patients experienced no emesis compared with 54% (European study) and 52% (US study) of patients treated with ondansetron 16 mg, the most effective dose. Similarly, 22% (European study) and 19% (US study) of placebo-treated patients experienced no nausea compared with 42% (European study) and 34% (US study) of ondansetron 16 mg-treated patients. All ondansetron doses in both studies were statistically superior to placebo (emesis p < or = 0.007; nausea p < or = 0.033). Slightly lower percentage differences in complete response between placebo and ondansetron for both nausea and emesis were observed for patients with a previous history of postoperative nausea and emesis compared with patients with no previous history, with ondansetron 16 mg being the most effective dose for both patient groups. In the US study, a slightly greater percentage of patients undergoing non-gynaecological surgery had no nausea and no emesis compared with patients undergoing gynaecological surgery in both the placebo and ondansetron treatment groups. Again, ondansetron 16 mg was the most effective dose in both surgery types. Ondansetron was well tolerated, with only headache being reported as a significant problem in both studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗